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101.
Dr. Mélissa Degardin Dr. Sharon Wein Dr. Jean‐Frédéric Duckert Marjorie Maynadier Dr. Alexandre Guy Dr. Thierry Durand Prof. Roger Escale Dr. Henri Vial Dr. Yen Vo‐Hoang 《ChemMedChem》2014,9(2):300-304
Plasmodium falciparum is responsible of the most severe form of malaria, and new targets and novel chemotherapeutic scaffolds are needed to fight emerging multidrug‐resistant strains of this parasite. Bis‐alkylguanidines have been designed to mimic choline, resulting in the inhibition of plasmodial de novo phosphatidylcholine biosynthesis. Despite potent in vitro antiplasmodial and in vivo antimalarial activities, a major drawback of these compounds for further clinical development is their low oral bioavailability. To solve this issue, various modulations were performed on bis‐alkylguanidines. The introduction of N‐disubstituents on the guanidino motif improved both in vitro and in vivo activities. On the other hand, in vivo pharmacological evaluation in a mouse model showed that the N‐hydroxylated derivatives constitute the first oral bioprecursors in bis‐alkylguanidine series. This study paves the way for bis‐alkylguanidine‐based oral antimalarial agents targeting plasmodial phospholipid metabolism. 相似文献
102.
Synthesis,Chiral Separation,Absolute Configuration Assignment,and Biological Activity of Enantiomers of Retro‐1 as Potent Inhibitors of Shiga Toxin 下载免费PDF全文
Dr. Hajer Abdelkafi Dr. Aurélien Michau Alexandra Clerget David‐Alexandre Buisson Dr. Ludger Johannes Prof. Daniel Gillet Dr. Julien Barbier Dr. Jean‐Christophe Cintrat 《ChemMedChem》2015,10(7):1153-1156
The Shiga toxin (Stx) family is composed of related protein toxins produced by the bacteria Shigella dysenteriae and certain pathogenic strains of E. coli. No effective therapies for Stx intoxication have been developed yet. However, inhibitors that act on the intracellular trafficking of these toxins may provide new options for the development of therapeutic strategies. This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of Retro‐1, a compound active against Stx and other such protein toxins. Retro‐1 works by inhibiting retrograde transport of these toxins inside cells. In vitro experiments proved that the configuration of the stereocenter at position 5 is not crucial for the activity of this compound. X‐ray diffraction data revealed (S)‐Retro‐1 to be slightly more active than (R)‐Retro‐1. 相似文献
103.
Ali El Hafidi Bruno Martin Alexandre Loredo Eric Jego 《Mechanical Systems and Signal Processing》2010,24(7):2198-2209
This study is composed of three essential parts. The first part describes an indirect semi-experimental method which is used to reconstruct the excitation force of an operating diesel engine from the acceleration data measured at the mounting points. These internal forces can not be directly measured with force sensors; they have to be derived from the dynamic deformation of the engine support, so a theoretical analysis is carried out to derive the equations for the force re-construction.The second part deals with prevention of low frequency vibration of the powertrain from spreading to the rest of the vehicle. Three uncoupling techniques are used to minimize these vibrations. The first technique reduces the non-diagonal elements of stiffness matrix. The second technique uses the elastic axes decoupling criterion. The third technique uncouple the torque roll axis (TRA) by using the previously determined excitation efforts.In the third part, numerical and experimental results are discussed. The solicitations deducted and the positions of mounts allowing decoupling of the powertrain are presented. 相似文献
104.
Electrical contact resistance between stainless steel bipolar plate and carbon felt in PEFC: A comprehensive study 总被引:1,自引:0,他引:1
Johan André Laurent Antoni Jean-Pierre Petit Eric De Vito Alexandre Montani 《International Journal of Hydrogen Energy》2009
Bipolar plate represents a key component of Proton Exchange Membrane Fuel Cell (PEFC) with several essential functions, among them the electric connection of elementary cells. Usually made of graphite, this component is studied worldwide in order to develop a commercially viable alternative: different ways have been being investigated, and to date, despite corrosion issues, stainless steel (SS) appears as a good candidate material, but its Electrical Contact Resistance (ECR) can reach unacceptable values when exposed to PEFC environment. This paper offers a comprehensive study of the parameters acting on ECR when using uncoated SS in PEFC: roughness, which influences the surface contact area with carbon baking, bulk composition of the alloy, which influences only partly the nature of passive films, and the composition and structure of passive films, strongly modified by surface treatments and ageing conditions. 相似文献
105.
Alexandre Caboussat Sébastien Boyaval Alexandre Masserey 《Computing and Visualization in Science》2011,14(8):401-417
The numerical simulation of three-dimensional dam break flows is discussed. A non-hydrostatic numerical model for free-surface flows is considered, which is based on the incompressible Navier–Stokes equations coupled with a volume-of-fluid approach. The numerical results obtained for a variety of benchmark problems show the validity of the numerical approach, in comparison with other numerical models, and allow to investigate numerically the non-hydrostatic three-dimensional effects, in particular for the usual test cases where hydrostatic approximations are known analytically. The numerical experiments on actual topographies, in particular the Malpasset dam break and the (hypothetical) break of the Grande-Dixence dam in Switzerland, also illustrate the capabilities of the method for large-scale simulations and real-life visualization. 相似文献
106.
Alexandre Boucher 《Computers & Geosciences》2009,35(6):1151-1158
Using a complex training image (TI) for the single normal equation simulation (SNESIM) algorithm results in poor simulated realizations since that image contains trends and location specific patterns. By pooling all the TI patterns in a single search tree and not recording the relative locations of those patterns, some critical features of these complex TIs are lost.The search tree partitioning approach subdivides a large TI into imbricated, homogeneous, smaller images, called partition classes. Each of these partition classes has a corresponding search tree that can be utilized by the SNESIM algorithm. These partition classes are obtained by processing the TIs with spatial filters that are pattern sensitive. The resulting filter scores are then clustered into partition classes. All patterns within a partition class are recorded by a search tree; there is one tree per partition class. At each pixel along the simulation path, the partition class is retrieved first and used to select the appropriate search tree. That search tree contains the patterns relevant to that partition class.In practice, the partitioning approach adds flexibility in choosing a TI. TIs that were easier to obtain but traditionally too complex for simulation can now be considered as input to SNESIM. In many cases, it also significantly increases the simulation speed by searching a vector of smaller trees instead of a single large one. A plugin for the SGeMS software is provided. 相似文献
107.
Mr. Alain Froment Mr. Pascal Gautier Mr. Alexandre Nussbaumer Mr. Alec Griffiths 《Journal für Verbraucherschutz und Lebensmittelsicherheit》2011,6(2):277-281
Some mycotoxins are produced by several Fusarium species during cultivation and are found in wheat and maize grain. Since 2000, Syngenta has organised a large field survey. Agronomic and climatic data and grain samples have been collected for mycotoxin analysis in France and Belgium. The importance of the agroclimatic factors and their interactions on the mycotoxin levels in grain has been estimated. The climate around flowering stage is the major factor for deoxynivalenol (DON) in wheat. The main agronomic criteria are residue management and the variety sensitivity to this mycotoxin. For DON, zearalenone and fumonisins in maize, the climate from flowering stage until harvest is the major factor. Then, according to each mycotoxin, the main agronomic criteria are the harvest condition (date and grain moisture), the corn borer infestation and the variety sensitivity to these mycotoxins. Over the years, the database has been used to define models to predict the mycotoxin risk before harvesting. Grain purchasers enter the required agronomic data via the Syngenta Internet site and define their grain purchasing areas. They also define the flowering period for wheat and corn borer infestation for maize. After calculation which integrates climatic data, the purchasers receive reports with forecasts of mycotoxin levels. Prediction is based on different agro-climatic statistical models specifically configured according to the different regions of production in France and Belgium. This approach is called Qualimètre? and was the first service in France and Belgium to forecast the grain mycotoxin level for wheat in 2004 and maize in 2006. 相似文献
108.
The invasive green alga, Caulerpa taxifolia, that has spread rapidly after its introduction into the Mediterranean and the North American Pacific, reacts to wounding by transforming its major metabolite caulerpenyne (1). This wound-activated reaction involves the transformation of the bis-enol acetate moiety of 1, releasing reactive 1,4-dialdehydes. The ability to perform this transformation is found also in both the noninvasive Mediterranean C. prolifera and the invasive C. racemosa. Trapping experiments, as well as transformation of the model substrate geranyl acetate, suggest that all three investigated Caulerpa spp. rely on esterases that act upon wounding of the algae by subsequently removing the three acetate residues of caulerpenyne. The resulting reactive 1,4-dialdehyde oxytoxin 2 (9) can be identified by liquid chromatography–mass spectrometry and is unstable in the wounded tissue. Caulerpenyne transformation occurs rapidly, and severe tissue damage caused degradation of more than 50% of the stored caulerpenyne within 1 min in all three algae. Prevention of the enzymatic reaction before extraction, by shock freezing the tissue with liquid nitrogen, was used for the determination of the caulerpenyne content in intact algae. It gives about twofold higher values compared to an established methanol extraction protocol. The speed and mechanism of the wound-activated transformation, as well as the caulerpenyne content in intact tissue of invasive and noninvasive Caulerpa spp., are comparable. Thus, this enzymatic , transformation, despite being fast and efficient, is likely not the key for the success of the investigated invasive species. 相似文献
109.
Using the measures of initial reaction rate, a kinetic-photometric method is developed that uses the reaction of Diquat with H2O2 in basic medium. The reaction rate is very high and therefore the stopped-flow mixing technique is required in order to make kinetic measurements. The reaction rate is obtained in 20 s after the reactants are mixed and it allows the simple application of the method proposed to the routine analyses. The sensitivity of the method is very high being the detection limit 0.44 microgmL(-1) and the application range between 1 and 16 microgmL(-1). The time of measure per sample is 90s. The proposed kinetic-photometric method has been applied to the direct determination of this compound in river water, in the water of laundry of the olives, and in a commercial product. The results are very acceptable. 相似文献
110.
Alexandre Yakovlev Luciano Lavagno Alberto Sangiovanni-Vincentelli 《Formal Methods in System Design》1996,9(3):139-188
Characterization of the behavior of an asynchronous system depending on the delay of components and wires is a major task facing designers. Some of these delays are outside the designer's control, and in practice may have to be assumed unbounded. The existing literature offers a number of analysis and specification models, but lacks a unified framework to verify directly if the circuit specification admits a correct implementation under these hypotheses.Our aim is to fill exactly this gap, offering both low-level (analysis-oriented) and high-level (specification-oriented) models for asynchronous circuits and the environment where they operate, together with strong equivalence results between the properties at the two levels. One interesting side result is the precise characterization of classical static and dynamic hazards in terms of our model. Consequently the designer can check the specification and directly decide if the behavior of any implementation will depend, e.g., on the delays of the signals described by such specification.We also outline a design methodology based on our models, pointing out how they can be used to select appropriate high and low-level models depending on the desired characteristics of the system. 相似文献